Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial. in Nature communications / Nat Commun. 2025 Mar 23;16(1):2846. doi: 10.1038/s41467-025-58179-6.

2025
AO Cuneo

Tipo pubblicazione

Multicenter Study

Autori/Collaboratori (25)Vedi tutti...

Loges S
German-Cancer-Research-Center-(DKFZ)-Hector Cancer Institute, University Medical Center Mannheim, Mannheim, Germany. s.loges@dkfz-heidelberg.de.
Heuser M
Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany. s.loges@dkfz-heidelberg.de.
Chromik J
Department of Personalized Oncology, University Hospital Mannheim, and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. s.loges@dkfz-heidelberg.de.

et alii...

Abstract

Beyond first line, the prognosis of relapsed/refractory (R/R) acute myeloid leukemia (AML) patients is poor with limited treatment options. Bemcentinib is an orally bioavailable, potent, highly selective inhibitor of AXL, a receptor tyrosine kinase associated with poor prognosis, chemotherapy resistance and decreased antitumor immune response. We report bemcentinib monotherapy and bemcentinib+low-dose cytarabine combination therapy arms from the completed BerGenBio-funded open-label Phase 1/2b trial NCT02488408 ( www.clinicaltrials.gov ), in patients unsuitable for intensive chemotherapy. The primary objective in the monotherapy arm was identification of maximum tolerated dose with secondary objectives to identify dose-limiting toxicities, safety and efficacy, and bemcentinib pharmacokinetic profile. In the combination arm, the primary objective was safety and tolerability, with efficacy and pharmacokinetics as secondary objectives. Safety and tolerability were based on standard clinical laboratory safety tests and Common Terminology Criteria for Adverse Events version 4. Bemcentinib monotherapy (32 R/R, 2 treatment-naïve AML and 2 myelodysplasia patients) was well-tolerated and a loading/maintenance dose of 400/200?mg was selected for combination treatment, comprising 30 R/R and 6 treatment-naïve AML patients. The most common grade 3/4 treatment-related adverse events were cytopenia, febrile neutropenia and asymptomatic QTcF prolongation, with no grade 5 events reported. In conclusion, bemcentinib+low-dose cytarabine was safe and well tolerated.

Accesso banca dati bibliografica

PMID : 40122885

DOI : 10.1038/s41467-025-58179-6

Keywords

Humans; Cytarabine/administration & dosage/adverse effects/therapeutic use/pharmacokinetics; Leukemia, Myeloid, Acute/drug therapy; Male; Middle Aged; Female; Aged; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use/pharmacokinetics/administration & dosage; Adult; Axl Receptor Tyrosine Kinase; Maximum Tolerated Dose; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors; Proto-Oncogene Proteins/antagonists & inhibitors;